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Biomedical subjects

M Haas

Publications and source records attributed to M Haas.

At least 307 records · Page 17Linked to original sources
PubMed1980

Genomic masking and rescue of dual-tropic murine leukemia viruses: role of pseudotype virions in viral lymphomagenesis.

The kinetics of genomic masking of nondefective dual-tropic murine leukemia viruses (MuLV) by ecotropic MuLV in mixedly infected mouse cells was studied. The ratio of virus infection (ecotropic to dual-tropic) determined the kinetics of genomic masking. Some dual-tropic virus isolates could be masked routinely (i.e., converted to virions containing a dual-tropic genome and possessing the ecotropic host range) at all ratios of initial infection of mixedly infected mouse cells. The masked genomes could be rescued as infectious viruses of dual-tropic genotype and host range by an infectious center assay of the infected mouse cells on mink lung cells. Infectious center rescue of masked dual-tropic MuLV took place readily, even from cells that had been kept in continuous culture for many months after the onset of genomic masking. Some dual-tropic virus clones did not undergo genomic masking at any infection ratio with ecotropic virus. Nevertheless, such mixedly infected cultures also gave rise to phenotypically mixed virions, which contained a dual-tropic genome and had an ecotropic host range. (The phenotypically mixed virions found among the progeny of mixedly infected mouse cells were not pseudotypes, as both types of viruses were genetically nondefective, nor was the process leading to their generation a bona fide phenotypic mixing [Fischinger et al., Science 201:457-459, 1978]. Nevertheless, in this paper we use the terms pseudotype and phenotypic mixing because of the lack of a better description.) The lymphomagenic potential of dual-tropic lymphomagenic MuLV was compared with that of phenotypically mixed virions possessing an ecotropic host range and with that of a simple mixture of dual-tropic and ecotropic viruses. The phenotypically mixed pseudotype virions were more potent lymphoma inducers than were those of dual-tropic, cloned genotype. Inoculation of a simple mixture of the viruses did not increase dual-tropic virus tumorigenicity. The reason for this was probably the highly efficient inactivation of dual-tropic virus by oncovirus-inactivating factor, which is present in normal mouse serum and did not inactivate the phenotypically mixed virions. Simple mixtures of dual-tropic lymphomagenic and ecotropic virus preparations behaved like the cloned, dual-tropic virus in vivo and were equally sensitive to oncovirus-inactivating factor in vitro. Thus, phenotypic mixing of dual-tropic and ecotropic MuLV with or without concomitant genomic masking may be a highly significant phenomenon in naturally occurring lymphomagenesis. It may also be important to use phenotypically mixed viruses in the procedures used for in vivo testing of lymphomagenic dual-tropic MuLV isolates.

Animals↗
PubMed1980

Abrogation of radiation leukemia virus-induced lymphomagenesis by antisera to thymotropic but not to ecotropic or dual-tropic viruses.

Leukemia induction by culture-grown thymotropic radiation leukemia virus or by tumor-derived virus present in cell-free tumor extracts was abrogated by incubation of either virus with anti-thymotropoc virus serum, but not by antiserum raised against ecotropic or dual-tropic (mink cell focus-inducing type) viruses that were isolated from radiation leukemia virus-induced thymic leukemias. Thus, virus similar or identical to the cultured thymotropic leukemogenic species may also be the major biologically active principle in tumor-derived extracts, even though the latter also contain viruses of the dual-tropic, mink cell focus-inducing type class.

Animals↗
PubMed1979

Reticulum cell neoplasms induced in C57BL/6 mice by cultured virus grown in stromal hematopoietic cell lines.

Thirty-one adherent cell lines have been established from the spleens, lymph nodes, and bone marrow of C57BL/6 mice carrying radiation leukemia virus (Duplan isolate)-induced reticulum cell neoplasms (RCN). The cell lines had a stable epithelial or fibroblastoid morphology, Supernatant virus from these lines induced splenic and lymph node RCN in 100% of inoculated C57BL/6 mice within 30 days. The disease was generalized and involved many organs. The monolayer cells themselves were not tumor cells and induced RCN through infection of the host with RCN virus. Simultaneous inoculation of in vitro-grown RCN-inducing virus any thymic lymphosarcoma virus induced each disease independently with unaltered incidence, latency period, and organ involvement; no mutual enhancement or inhibition was found, thus two separate mechanisms of action were indicated. Reextraction of the viruses from spleen, lymph nodes, and thymus gland indicated the specific organotropism of each agent. All the adherent cell lines that were derived from hematopoietic tissues produced ample, potent RCN-inducing virus. This high success rate suggests that in the hematopoietic organs the stromal, fibroblastoid cells are a natural habitat for the RCN-inducing virus. The RCN-inducing virus species may well be synthesized in these hematopoietic stromal cells. RCN-inducing virus from culture supernatants contained high-titer infectious ecotropic and xenotropic virus that was titrated. The cultures are being used to clone the RCN-inducing virus and to establish the virologic and molecular properties that endow it with specific RCN-inducing capacity.

Animals↗
PubMed1978

Genetic analysis of in vitro leukemogenesis induced by thymus epithelial reticulum cells transmitting murine leukemia viruses.

Lymphatic leukemia developed in C57BL/6 mice following inoculation of normal thymocytes that and been co-cultured on leukemic thymus epithelial reticulum monolayer cells. Using thymocytes genetically marked in Ly membrane antigens, we showed that the thymomas which developed were produced by the co-cultured thymocytes rather than by leukemic cells derived from the monolayer. Thus, leukemogenic conversion of normal thymocytes took place in vitro. Inoculation of cultured leukemic thymus epithelial reticulum monolayer cells (LTER) gave rise mainly to reticulum cell sarcomas and myeloid leukemias, rather than to lymphatic leukemias (which developed following inoculation of thymocytes that had been cultured on the LTER monolayers). Thus LTER cells may themselves be tumor cells capable of producing RCNA (reticulum cell neoplasm type A) or myeloid tumors in addition to their ability to convert normal thymocytes into leukemic cells.

Animals↗
PubMed1978

Radioimmunoassayable plasma vasopressin associated with surgery.

Plasma vasopressin concentration was measured by radioimmunoassay before, during, and after anesthesia and surgery in ten subjects. During the short period between the onset of anesthesia and the start of operation, small elevations of vasopressin level were noted. Surgery itself was associated with significant elevations of up to 82 pg/ml. Highest levels of vasopressin were noted with major intra-abdominal surgery and lowest levels with limb surgery. The immediate postoperative period was marked by plasma vasopressin levels that were often higher than during surgery itself. Levels gradually fell to their preoperative state after three to four days. The elevated levels of vasopressin can be associated with oliguria and excessive water retention. Among the possible mechanisms for the stimulus to vasopressin secretion are pain, stress, positive pressure respiration and anoxia. This study confirms by radioimmunoassay the changes in plasma vasopressin level with surgery that have been previously described by bioassay.

Anesthesia, General↗
PubMed1978

Lithium transport pathways in human red blood cells.

In human red cells, Li is extruded against its own concentration gradient if the external medium contains Na as a dominant cation. This uphill net Li extrusion occurs in the presence of external Na but not K, Rb, Cs, choline, Mg, or Ca, is ouabain-insensitive, inhibited by phloretin, and does not require the presence of cellular ATP. Li influx into human red cells has a ouabain-sensitive and a ouabain-insensitive but phloretin-sensitive component. Ouabain-sensitive Li influx is competitively inhibited by external K and Na and probably involves the site on which the Na-K pump normally transports K into red cells. Ouabain does not inhibit Li efflux from red cells containing Li concentrations below 10 mM in the presence of high internal Na or K, whereas a ouabain-sensitive Li efflux can be measured in cells loaded to contain 140 mM Li in the presence of little or no internal Na or K. Ouabain-insensitive Li efflux is stimulated by external Na and not by K, Rb, Cs, choline, Mg, or Ca ions. Na-dependent Li efflux does not require the presence of cellular ATP and is inhibited by phloretin, furosemide, quinine, and quinidine. Experiments carried out in cells loaded in the presence of nystatin to contain either only K or only Na show that the ouabain-insensitive, phloretin-inhibited Li movements into or out of human red cells are stimulated by Na on the trans side and inhibited by Na on the cis side of the red cell membrane. The characteristics of the Na-dependent unidirectional Li fluxes and uphill Li extrusion are similar, suggesting that they are mediated by the same Na-Li countertransport system.

Adenosine Triphosphate↗
PubMed1977

Abnormal lithium and sodium transport in erythrocytes of a manic patient and some members of his family.

This paper compares the transport of Li(+) and Na(+) in erythrocytes from a patient with mania and from members of his family to that in erythrocytes from normal humans. In normal human erythrocytes, Li(+) is transported by at least three operationally distinct pathways: one inhibited by ouabain (ouabain-sensitive), one by phloretin (phloretin-sensitive), and one not inhibited by either compound (insensitive). Li(+) can be driven up its electrochemical potential gradient by an oppositely directed electrochemical potential gradient for Na(+)-i.e., Li(+)/Na(+) counterflow can occur-through the phloretin-sensitive pathway but not through the other two pathways. Because ouabain-sensitive Li(+) transport is negligible under physiological conditions, Li(+) distribution between erythrocytes and plasma in vivo depends mainly on the balance between Li(+)/Na(+) counterflow and the insensitive pathway(s) of Li(+) transport. The steady-state ratio of Li(+) concentration in the erythrocytes to that in the plasma of the patient was between 2 and 3 times higher than the comparable ratio in normal persons. The phloretin-sensitive Li(+)/Na(+) counterflow system was almost absent in the erythrocytes of the patient. Furthermore, unlike those from normal individuals, the patient's erythrocytes showed no external Li(+)-stimulated, phloretin-sensitive, ouabain-insensitive Na(+) efflux. The magnitudes of the ouabain-sensitive and insensitive pathways for Li(+) transport in the patient's erythrocytes were within normal limits. The decreased Li(+)/Na(+) counterflow in the patient's erythrocytes was probably not due to the presence of an inhibitor in the plasma of the patient but rather to an intrinsic defect in the erythrocytes. Because the father and several siblings of the patient showed a similar abnormality in erythrocyte Li(+)/Na(+) transport, it is probable that this defect is inherited.

Adolescent↗
PubMed1977

Transient virus expression during murine leukemia induction by X-irradiation.

Most X-irradiation-induced thymomas in C57BL/6 mice are virus-free when assayed by immunofluorescence for the gs antigen (gsa) of murine leukemia virus (MuLV). Virus was induced transiently in bone marrow cells and later appeared in thymus cells. Six to 7 weeks post irradiation, thymocytes and bone marrow cells were MuLV gsa-negative and remained negative for the lifetime of most animals, whether or not they contracted overt leukemia. During the period when MuLV gsa-positive bone marrow cells were found, XC-positive syncytia-producing bone marrow cells were also found. Virus information was expressed, therefore, for a limited duration, long before any signs of leukemia in the animals were evident. MuLV gsa-positive thymocytes taken from mice 4 weeks after X-irradiation were cocultivated with a series of indicator cells. B-tropic virus, in addition to a xenotropic virus, was isolated from these cells. Ecotropic virus was not found in normal mouse thymocytes, in irradiated thymocytes a few days after termination of the X-irradiation sequence, or in most primary thymomas. All thymocytes produced only xenotropic virus in the cocultivation assays. Expression of the ecotropic virus was, therefore, transient, as assayed by immunofluorescence, XC syncytia formation, and virus isolation from MuLV gsa-positive thymus cells.

Animals↗
PubMed1977

Leukemogenesis in vitro induced by thymus epithelial reticulum cells transmitting murine leukemia viruses.

The role of the thymus in induction of leukemia was studied in vitro. Curltivation of normal thymus cells on thymus epithelial reticulum cell monolayers that had been grown from radiation leukemia virus-induced leukemic thymuses rendered the thymocytes leukemic. C57BL/6 thymocytes were cultivated for 3 days on leukemic thymus reticulum monolayers, and 106 thymocytes were injected i.p. into young adult C57BL/6 mice. After 3 to 4 weeks all mice died of disseminated lymphatic leukemia. Mice given thymocytes that had been cultivated on thymus epithelial reticulum monolayers from normal mice did not develop lymphomas. The leukemic thymus epithelial reticulum cells were shown to produce thymotropic as well as ecotropic and xenotropic radiation leukemia virus. (Thymotropic virus has affinity for thymus lymphocytes but noes not infect fibroblasts.) The cells were brightly positive for murine leukemia virus group-specific antigen in immunofluorescence tests. Leukemic thymus epithelial reticulum cells produced ample infectious exotropic virus in the culture supernatant, although the cells were negative in the XC syncytia test. Upon infection of mouse fibroblasts with ecotropic virus produced by the leukemic reticulum cells, XC syncytia were readily obtained. Thymocytes that were cultivated on leukemic thymus reticulum cells became positive for murine leukemia virus group-specific antigen and produced syncytia in the XC test. Thus, in vitro lymphomagenesis of the thymocytes that were cultured on leukemic thymus reticulum cells was associated with their infection with thymotropic and ecotropic radiation leukemia virus.

Animals↗
PubMed1977

Medical student education in psychiatry.

The authors interpret data obtained from 99 medical schools which submitted grant applications for support of either undergraduate psychiatric education programs or human behavior programs. They tentatively conclude that high-quality programs for teaching medical students psychiatry are characterized by a well-rounded faculty, a psychodynamic orientation, a greater commitment to medical student education than to resident training, varied teaching methods, enthusiastic student response, and systematic evaluation that produces change in subsequent years.

Attitude of Health Personnel↗
PubMed1976

Pulsed nuclear magnetic resonance study of 17O from H217O in rat lymphocytes.

Lymphocytes obtained from thymus glands of normal rats and culture lines of malignant rat thymocytes were enriched with H217O. The longitudinal and transverse relaxations of the 17O were determined separately in samples of packed cells and supernatant solutions. The longitudinal relaxation of intracellular 17O of fresh viable lymphocytes was nonexponential, becoming simply exponential with eventual necrosis. The rate of spin-lattice relaxation (1/T1) was fitted by a sum of two exponentials. The average mole fraction of the molecules subject to the slower relaxation rate (1/T1s) was two-thirds of the total water. Lowering the Larmor frequency (omega) from 7.72 to 4.36 MHZ increased the faster component (1/T1f) by 12% without altering (1/T1s). The value of the single exponential decay of the nonviable cells was not appreciably different from the initial rate of relaxation of the fresh cells. Similar results were obtained in studies of the transverse relaxation rates. The simplest interpretation is that two-thirds of the cell water is located within the nucelus and is characterized by a slower rate of relaxation than the one-third of the cell water in the cytoplasm because of the different macromolecular compositions of the two-subcellular compartments. The malignant lymphocytes were characterized by prolonged values for the slow and fast components of both the longitudinal and transverse relaxations of 17O.

Animals↗
PubMed1976

[Comparative studies on the teaching of oral pathology].

This is a self-assessment of teaching effectiveness for teacher, students and teaching-material as well. A curriculum of oral patholology was created and prepared as syllabus, lectures and audiovisual aids. In order to estimate and compare the eductional achievements of different systems, a series of written multiple choice questions were prepared. Only items with an index of discrimination of more than 0,25 were used. The average index was 0,5. The results of a short-term experimetn (1 hour) shows that a teaching sequence in the conventional lecture style was most effective in transmitting knowledge (72% of maximum), audiovisual aids rating second (63%), followed by individual homework study using printed material (48%). The differences were statistically significant in most experiments. In the second type of experiment (long-term-experiment) we registered the time the students spent with lectures over a period of six months. When permitted to chose between the different systems the students preferred the audiovisual method to the lectures. Individual testing of these students shows a positive correlation between knowledge acquired and time spent with the audiovisual machines.

Audiovisual Aids↗
PubMed1975

In vitro infection of lymphoid cells by thymotropic radiation leukemia virus grown in vitro.

Murine lymphoid cells were infected in vitro with purified leukemogenic radiation leukemia virus (RadLV) produced by virus-induced lymphoblast cell lines. Thymocytes were shown to be highly susceptible to infection by the virus, whereas murine or other fibroblasts were refractory to it. Murine bone marrow and spleen cells were shown to be much less sensitive to infection by this thymotropic RadLV. By comparison, a B-tropic RadLV isolate (RadLV), propagated on a mouse fibroblast cell line, was noninfectious for lymphoid cells but infected fibroblasts. A correlation was shown to exist between in vitro infection of thymocytes, as assayed by immunofluorescence, and in vivo leukemogenicity of the thymotropic RadLV. This constitutes a rapid in vitro test for in vivo leukemogenicity of a natural lymphatic leukemia virus.

Animals↗